During hypo-and hyperbaric decompression, gas supersaturation of tissues or blood can cause bubbles to form there with serious medical consequenses. The growing use of dysbaric environments by man has made this problem of decompression sickness increasingly important. The objective of the present study is to increase the understanding of the early etiology of decompression sickness, an area which has received little attention in the past. For example, the biophysical basis for the very high in vivo susceptibility for bubble formation has not been established, and essential information is lacking as to where the bubbles form. Our general approach is to first investigate the basic phenomena associated with bubble formation in relatively simple biological systems, and then proceed to systems of higher morphological complexity. During the past phase of our studies, some much needed information has been obtained on gas bubble nucleation in aqueous solutions in vitro, in cells and in primitive organisms. During the next phase, the factors that govern the formation of bubbles in single cells and primitive organisms will be further examined. Specifically, our aims are to (1) identify the probable mechanisms for bubble formation, such as gaseous nuclei, mechanical forces, or interfaces, in organisms that have especially low intra- or extravascular gas supersaturation tolerances, but are relatively simple morphologically; (2) determine the role of hydrophobic interfaces in intracellular bubble formation; and (3) assess the effect of various physical factors on the nucleation of bubbles in vitro, and correlate this information with that obtained in vivo. The methods to be used include microscopic observations and high speed cinephotomicrographic recordings of events during decompression while manipulating the gas saturations and the rates of compression and decompression; a major part of the instrumentation and the procedures have been developed. The results obtained will be used to formulate new approaches and to reevaluate existing concepts relating to formation of bubbles in vivo. Our long range goal is to aid in the prevention and treatment of decompression sickness by contributing to the development of better hyperbaric gas mixtures and decompression procedures.